EPLIN stabilizes cell–cell adhesion complexes to facilitate TGF-β1–induced fibroblastic differentiation of human periodontal ligament stem cells

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ID: 329939
2026
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Abstract
OBJECTIVES: Periodontal ligament stem cells (hPDLSCs) are essential for periodontal regeneration, yet the molecular mechanisms governing their differentiation into functional fibroblasts remain poorly understood. This study aimed to identify novel regulatory molecules of PDL fibroblastic differentiation and elucidate the role of Epithelial Protein Lost In Neoplasm (EPLIN) in the fibroblastic differentiation. METHODS: hPDLSCs were differentiated into PDL fibroblasts using TGF-β1. A novel antibody (anti-LG45) identified EPLIN as a target antigen. Functional roles of EPLIN were investigated through siRNA-mediated depletion and ectopic overexpression. Phalloidin staining for F-actin, and co-immunoprecipitation were performed to analyze adherens junction integrity. RESULTS: TGF-β1 treatment successfully induced fibroblastic differentiation, as evidenced by significant increases in fibroblastic marker expressions, which were abolished by the TGF-β receptor inhibitor SB-431542. A novel Anti-LG45 antibody was found to specifically recognize EPLIN in differentiated PDL fibroblasts. EPLIN depletion significantly reduced the fibroblastic differentiation and disrupted the typical elongated morphology of PDL fibroblasts. Mechanistically, EPLIN depletion led to filament fragmentation and cytoskeletal collapse, decoupled N-cadherin from the cytoskeleton, and accelerated cell proliferation. Conversely, ectopic overexpression of EPLIN-α or β was sufficient to inhibit proliferation and induce fibroblastic markers even without TGF-β1 stimulation. CONCLUSION: EPLIN is a key regulatory factor that stabilizes the linkage between the actin cytoskeleton and adherens junctions, maintaining the fibroblastic phenotype and preventing unscheduled proliferation in hPDLSCs. This study indicates the importance of cytoskeletal structural integrity in PDL differentiation. Under this circumstance, EPLIN serves as a regulator that maintains the fibroblastic differentiation state of hPDLSCs and prevents unscheduled proliferation.
Reference Key
openalex_W7214287375 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors A-Hyeong Choi, Seon-Yle Ko, Young-Joo Jang
Journal stem cells international
Year 2026
DOI
10.1093/stmcls/sxag053
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